Jae-Won Jung¹, Na-Hyun Kim¹, Yong Heo^{2, 3}, Jong-Sik Jin⁴, Young-A Lee^1,

Capsanthin, from paprika (Capsicum annuum), is a carotenoid with an orange-red pigment. It possesses pharmacological effects such as anti-obesity, antidiabetic, and anticancer activities. However, whether capsanthin affects the dopaminergic system remains unclear. Herein, we investigated its impact on the dopaminergic system and dopamine-associated social behaviors. Cerebral cortical neurons were cultured and treated with capsanthin (3, 30, and 300 μg/ml). Immunostaining was used to investigate dopamine-related protein expression. Healthy, wild-type ICR mice were used for animal experiments. Capsanthin (30 mg/kg) was orally administered via a gavage feeding tube from postnatal days 21 to 28. Behavioral tests, including motility, social-preference, and social-interaction tests, were conducted on juvenile mice from postnatal days 28 to 35 and on adult mice from postnatal day 56 onwards. Capsanthin treatment resulted in significantly reduced expression of dopamine receptors D3 and D5 in cerebral cortical neurons. Capsanthin administration induced a significant elevation in social preference during both the juvenile and adult periods, whereas enhancement of social interaction was observed only during the adult period. This study suggests that capsanthin enhanced social behavior via the dopaminergic system, especially through dopamine receptors D3 and D5. These findings propose capsanthin as a potential candidate for the amelioration of dopamine-associated psychiatric disorders, including schizophrenia and major depressive disorder.

Capsanthin, dopamine, dopamine receptor, locomotion, social preference, social interaction